Prolidase deficiency (PD) is a rare recessive disorder resulting from mutations in the
prolidase gene (PEPD); only 17 causative mutant alleles had been so far characterized.
Prolidase is a ubiquitous
enzyme that hydrolyses
dipeptides with C-terminal
proline or
hydroxyproline residues and indeed, lack of this
enzyme activity causes massive urine excretion of undigested iminodipeptides. The clinical manifestations of PD are widely variable, and include intractable
skin ulcers, unusual face, different degree of
mental retardation, and
recurrent infections. No definitive treatment is at present available.We report an 8-year girl with a typical PD
facies, normal intelligence, and recurrent deep ulcerations complicated by
infections. She was found to be compound heterozygous for two novel mutations in PEPD, c.1133delACG and c.1301delT, affecting the C-terminal end of the
enzyme where the active site is located. Given her life-threatening course, she underwent allogeneic
hematopoietic stem cell transplantation (HSCT) from her HLA-identical brother, confirmed heterozygous for the c.1133delACG allele. Successful engraftment was documented by full-donor chimerism. Posttransplant monitoring of erythrocyte
prolidase activity showed that the child had converted to a heterozygous pattern. Reduction of excreted urine
dipeptides, evaluated by capillary electrophoresis, supported the effectiveness of the treatment. Unfortunately the patient died on day +92 of
invasive fungal infection.Despite the unfavorable outcome, we provide the first evidence that HSCT has the potential to reverse some of the biochemical features of PD patients. The indication to transplant must be balanced against the clinical manifestation of individual patients.